Prediabetes and diabetes prevalence in the Workers’ Oral Health Study

Abstract

Objective

To examine the association between periodontitis, diabetes, and prediabetes, assessed by fasting plasma glucose (FPG).

Materials and methods

Workers' Oral Health Study is a cross-sectional survey conducted on a representative sample of the Spanish employed population including 5154 participants (59.5% men, aged 16–65). Examination of periodontal status assessed Community Periodontal Index (CPI) and clinical attachment levels (CAL). Biochemical determinations included fasting plasma glucose (FPG), triglycerides, and total cholesterol. Logistic regression analysis with adjustment for potential confounders was used to evaluate the association between periodontitis and abnormal glucose regulation.

Results

Ninety-five participants (2.2%) of the study population had diabetes, while 373 (8.8%) presented prediabetes. Prediabetes was not associated with CPI or CAL in fully adjusted multivariate logistic regressions models. Diabetes was significantly associated with subjects having a CPI 4 after adjustment for potential confounders (odds ratio OR = 1.9, 95% confidence interval (CI) 1.1–3.1). This association was stronger in subjects < 45 years (OR = 4.0, 95% CI 1.2–12.7).

Conclusion

Periodontitis was associated with diabetes mellitus, but not with prediabetes, in a representative sample of the Spanish employed population. The association was stronger for younger subjects, which emphasizes the need for early detection of diabetes in younger patients affected by periodontitis, particularly because periodontal therapy may help to improve glycemic control.

Clinical relevance

Periodontitis is associated with diabetes mellitus, having at the same time a negative effect on glycemic control. It is important to develop proper early diagnosis strategies for both conditions, particularly in young male adults.

https://ift.tt/2NB02Nh

Transcatheter mitral valve therapies

Abstract

Dr.O.P. Yadava, Editor-in-Chief, IJTC and Dr. V Bapat, Assistant Professor at Columbia University, New York, discuss issues related to slow development and uptake of transcatheter mitral valve replacement. Dr. Bapat stresses on the basic difference between transcatheter aortic and mitral valve interventions. He laments that issues related to mitral valve repair versus replacement and role of percutaneous MitraClip are still being hotly debated. He, however, is hopeful that technology shall evolve to make percutaneous options for secondary mitral regurgitation a viable proposition.

https://ift.tt/2H9nLmo

Opportunities and challenges for thoracic organ transplantation in government institutions

Abstract

The first successful heart transplant in India was performed by Panangipalli Venugopal on 3 August 1994 at the All India Institute of Medical Sciences, New Delhi. Twenty-five years later, only seven government institutions are performing heart transplants and only one government hospital has an established heart transplant program in India. Only one lung transplant has been performed in a government institution all over the country. This article reviews the history and current status of thoracic organ transplant in India. The authors discuss the factors responsible for the dismal progress of thoracic organ transplant in government hospitals, opportunities available in government institutions for widening the scope of transplant program, and the steps taken by the Government of India to improve healthcare in the country.

https://ift.tt/2tKARyx

Effect of temperature on thermal, mechanical and morphological properties of polypropylene foams prepared by single step and two step batch foaming process

Abstract

This study reports the influence of foaming temperature on morphological and thermo-mechanical characteristics of polypropylene (PP) foams prepared using two different methods of batch foaming at low saturation pressures. In the first method, involving single-step pressure-induced-foaming (PIF), the solid specimen was heated to different temperatures in a high-pressure vessel, and then saturated CO₂ under pressure. Depressurization then led to foaming. In the second method, involving a two-step temperature-induced-foaming (TIF), the solid specimen was saturated with pressurized CO₂ at room temperature for a specific period of time and then the CO₂ laden specimen was immersed in hot glycerol bath at different temperatures for foaming. SEM micrographs of the fractured foamed specimens were employed for measurement of cell-size distribution. The average cell sizes ranged between 3 and 310 μm in specimens obtained using PIF, while in case of foams prepared by TIF, the cell sizes ranged between 30 and 70 μm. The cell sizes achieved in TIF are significantly smaller and more uniform as compared to those in PIF foams. The density (0.393–0.186 g cm⁻³) of PIF foams was seen to decrease with increasing foaming temperature; in contrast, in case of TIF the density remained more or less unchanged around 0.43–0.47 g cm⁻³ with changes in foaming temperature. The foamed specimens were characterized in uniaxial compression; the stiffness (elastic and collapse moduli) and compressive strengths of both the PIF and TIF foams were seen to decrease with increase in cell-size. The magnitude of plateau-regime stresses within the compressive stress-strain response showed strong correlation with the foam cell-wall thickness. The crystallinity of the foamed specimens was observed to decrease with increase in foaming temperatures. The thermal stability of both PIF and TIF foams in general showed improvement compared with the PP matrix.

https://ift.tt/2GQU3n5

Natural woodlands hold more diverse, abundant, and unique biota than novel anthropogenic forests: a multi-group assessment

Abstract

Biodiversity sustained by natural ecosystems, particularly forests, provides ecosystem services essential to human well-being. However, many forests have been severely transformed, notably via monospecific plantations and the spread of invasive species. Given the extension of these novel anthropogenic forests (plantations and invasive copses), it is critical to know how they can support forest biodiversity, particularly in highly humanized biodiversity hotspots as the southwest Mediterranean Europe. Because the effects likely vary across taxonomic groups, such assessments require an integrative multi-group approach. Here, we evaluated the abundance, richness, and composition of shrubs, herbs, macrofungi, ground and flying arthropods, birds, small mammals, carnivores, and bats across the four most common forest types in Central Portugal, namely: natural oak woodlands (dominated by Quercus faginea Lam.) and anthropogenic forests, invasive Acacia dealbata Link copses, Pinus pinaster Aiton plantations (native), and Eucalyptus globulus Labill. plantations (exotic). Oak woodlands sustained higher abundance, diversity, and a unique species composition compared to the other forests, especially those dominated by exotic species. The greatest changes in biodiversity occurred in herbs and birds. Contrary to our expectations, species richness and composition of macrofungi and carnivores in acacia copses were similar to those of oak woodlands, revealing that groups respond differently to forest changes. The large-scale replacement of natural forests by novel anthropogenic forests has significant negative impacts in most, but not all groups, which should be actively considered for integrative conservation strategies.

https://ift.tt/2EoaR0N

Carnosic Acid Inhibits CXCR3 Ligands Production in IL-27-Stimulated Human Oral Epithelial Cells

Abstract

Carnosic acid, which is a bioactive compound isolated from rosemary, has various pharmacological effects. However, the anti-inflammatory effect of carnosic acid on periodontitis is still unknown. The aim of this study was to investigate the effect of carnosic acid on CXC chemokine receptor 3 (CXCR3) ligands, which are involved in Th1 cells migration and accumulation, production in interleukin (IL)-27-stimulated human oral epithelial cells (TR146 cells). Carnosic acid decreased CXC chemokine ligand (CXCL)9, CXCL10, and CXCL11 production in IL-27-stimulated TR146 cells in a dose-dependent fashion. Moreover, we disclosed that carnosic acid could suppress signal transducer and activator of transcription (STAT)1, STAT3, and protein kinase B (Akt) phosphorylation in IL-27-stimulated TR146 cells. Furthermore, STAT1, STAT3, and Akt inhibitors could suppress CXCR3 ligands production in IL-27-treated TR146 cells. In summary, carnosic acid could reduce CXCR3 ligands production in human oral epithelial cell by inhibiting STAT1, STAT3, and Akt activation.

https://ift.tt/2VryKeQ

Regulatory T Cells Could Improve Intestinal Barrier Dysfunction in Heatstroke

Abstract

Intestinal barrier dysfunction plays a pivotal role in multiorgan dysfunction during heatstroke (HS). Neutrophils are involved in intestinal inflammation and thus dampen the mucosal integrity. Regulatory T cells (Tregs) have been shown to orchestrate neutrophils and thus sustain mucosal integrity in miscellaneous inflammation-related diseases. However, whether Tregs are involved in HS-induced intestinal barrier dysfunction remains unknown. Thus, we investigated whether Tregs could alleviate intestinal barrier dysfunction in mice. We found that HS could induce intestinal injury and mucosal barrier dysfunction 0, 24, and 72 h after heat stress. Flow cytometry revealed an increase of neutrophil infiltration and a decrease of Treg frequencies in the small intestinal epithelium 72 h after heat stress. Treg depletion starting 2 days before HS exacerbated intestinal damage and mucosal barrier dysfunction. Adoptive transfer of Tregs at 0 h improved intestinal injury and mucosal barrier dysfunction at 72 h. The manipulation of Tregs affected the neutrophil frequencies in the small intestinal epithelium 72 h after heat stress. Our study demonstrated that Tregs could improve HS-induced intestinal barrier dysfunction, probably via modulation of neutrophils in the intestine of mice during HS.

https://ift.tt/2EFEwEm

Diagnosis and Treatment Patterns in Celiac Disease

Abstract

Celiac disease (CD) is an immune-mediated gastrointestinal (GI) disorder driven by innate and adaptive immune responses to gluten. Presentation of CD has changed over time, with non-GI symptoms, such as anemia and osteoporosis, presenting more commonly. With improved screening and diagnostic methods, the reported prevalence of CD has increased globally, and there is considerable global variation in diagnostic and treatment practices. The objective of this study was to describe the current state of CD diagnosis and treatment patterns. A targeted review of literature from MEDLINE, Embase, the Cochrane Library, and screening of relevant conference abstracts was performed. The generally recommended diagnostic approach is GI endoscopy with small bowel biopsy; however, in selected patients, biopsy may be avoided and diagnosis based on positive serology and clinical symptoms. Diagnosis often is delayed; the average diagnostic delay after symptom onset is highly variable and can last up to 12 years. Barriers to accurate and timely diagnosis include atypical presentation, lack of physician awareness about current diagnostic criteria, misdiagnosis, and limited access to specialists. Currently, strict adherence to a gluten-free diet (GFD) is the only recommended treatment, which is not successful in all patients. Only one-third of patients are monitored regularly following diagnosis. Unmet needs for CD include improvements in the accuracy and timeliness of diagnosis, and the development of treatments for both refractory CD and GFD nonresponsive CD. Further research should investigate the impact of education about gluten-free eating and the availability of gluten-free foods support adherence and improve outcomes in patients with CD.

https://ift.tt/2Sv4UV3

The effect of severe and moderate hypoxia on exercise at a fixed level of perceived exertion

Abstract

Purpose

The purpose of this study was to determine the primary cues regulating perceived effort and exercise performance using a fixed-RPE protocol in severe and moderate hypoxia.

Methods

Eight male participants (26 ± 6 years, 76.3 ± 8.6 kg, 178.5 ± 3.6 cm, 51.4 ± 8.0 mL kg^− 1 min^− 1 \(\dot {V}\) O_2max) completed three exercise trials in environmental conditions of severe hypoxia (F_IO₂ 0.114), moderate hypoxia (F_IO₂ 0.152), and normoxia (F_IO₂ 0.202). They were instructed to continually adjust their power output to maintain a perceived effort (RPE) of 16, exercising until power output declined to 80% of the peak 30-s power output achieved.

Results

Exercise time was reduced (severe hypoxia 428 ± 210 s; moderate hypoxia 1044 ± 384 s; normoxia 1550 ± 590 s) according to a reduction in F_IO₂ (P < 0.05). The rate of oxygen desaturation during the first 3 min of exercise was accelerated in severe hypoxia (− 5.3 ± 2.8% min^− 1) relative to moderate hypoxia (− 2.5 ± 1.0% min^− 1) and normoxia (− 0.7 ± 0.3% min^− 1). Muscle tissue oxygenation did not differ between conditions (P > 0.05). Minute ventilation increased at a faster rate according to a decrease in F_IO₂ (severe hypoxia 27.6 ± 6.6; moderate hypoxia 21.8 ± 3.9; normoxia 17.3 ± 3.9 L min^− 1). Moderate-to-strong correlations were identified between breathing frequency (r = − 0.718, P < 0.001), blood oxygen saturation (r = 0.611, P = 0.002), and exercise performance.

Conclusions

The primary cues for determining perceived effort relate to progressive arterial hypoxemia and increases in ventilation.

https://ift.tt/2XsKpfi

Bioaugmentation and Biostimulation of Total Petroleum Hydrocarbon Degradation in a Petroleum-contaminated Soil with Fungi Isolated from Olive Oil Effluent

Abstract

In degradation of total petroleum hydrocarbon, 35 isolates belonging to 11 genera were sanitized and 3 isolates as well as their consortium were initiated to be able to raise in association with petroleum hydrocarbon as sole source of carbon under in vitro circumstances. The isolated strains were grounded on internal transcribed spacer (ITS) rDNA sequence analysis. The fungal strains with the utmost potentiality to reduce petroleum hydrocarbon without emerging antagonistic activities were Aspergillus niger, Penicillium ochrochloron, and Trichodema viride. For fungal growth on petroleum hydrocarbon, P. ochrocholon gained weight of 44%, A. niger 49%, and T. viride 39% within the first 30–40 days. As compared to the controls, these fungi accumulated significantly higher biomass, produced extracellular enzymes, and degraded total petroleum hydrocarbon and A. niger strongly degraded total petroleum hydrocarbon with a degradation of about 71.19%. These observations with GC-MS data confirm that these isolates displayed rapid total petroleum hydrocarbon biodegradation within a period of 60 days and the half-life showed that A. niger was the shortest with t1/2 = 21.280 day⁻¹ corresponding to the highest percent degradation of 71.19% and first-order kinetic fitted into the present study. By multivariate analysis, five main factors were identified by factor analysis (FA). The first factor (F1) of the fungi species accounts for 20.0% which signifies that fungi species controls the degradation of petroleum variability and hierarchical cluster analysis (HCA) as a dendrogram with five observations and three variables shows two predominant clusters order cluster 1 > 2.

https://ift.tt/2GP5JXv

Comparative study on long-term stability in mandibular sagittal split ramus osteotomy: hydroxyapatite/poly- l -lactide mesh versus titanium miniplate

Abstract

Background

Resorbable devices have recently been adopted in the field of orthognathic surgery with controversies about their postoperative skeletal stability. Hence, we determined the long-term skeletal stability of unsintered hydroxyapatite/poly-l-lactic acid (HA/PLLA) mesh for osteofixation of mandibular sagittal split ramus osteotomy (SSRO), and compared it with that of titanium miniplate.

Methods

Patients were divided into resorbable mesh and titanium miniplate fixation groups. A comparative study of the change in the mandibular position was performed with preoperative, 1-day, 6-month, and 2-year postoperative lateral cephalograms.

Results

At postoperative 6 months—compared with postoperative 1 day, point B (supra-mentale) was significantly displaced anteriorly in the titanium-fixation group. Moreover, at postoperative 2 years—compared with postoperative 6 months, point B was significantly displaced inferiorly in the titanium-fixation. However, the HA/PLLA mesh-fixation group did not show any significant change with respect to point B postoperatively.

Conclusions

The HA/PLLA mesh-fixation group demonstrated superior long-term skeletal stability with respect to the position of mandible, when compared with the titanium-fixation group.

https://ift.tt/2EjKQzP

The Use of OJIP Fluorescence Transients to Monitor the Effect of Elevated Ozone on Biomass of Canola Plants

Abstract

The effects of elevated ozone (O₃) levels (80 ppb and 120 ppb) on photosynthetic efficiency and growth of canola plants were studied in open-top chambers. The chlorophyll a polyphasic fluorescence rise kinetics OJIP, stomatal conductance and Chlorophyll Content Index (CCI) were measured after 15 and 30 days of O₃ fumigation, as well as in control plants; biomass measurements were done only after 30 days with and without fumigation. Analysis of the OJIP kinetics by the JIP-test led to the calculation of several photosynthetic parameters and the total Performance Index (PI_total). The decline of PI_total under the 80 ppb O₃ treatment was due to a lower density of reaction centres (RC/ABS), while the notable decline under the 120 ppb treatment was found to be due both to a further decline of RC/ABS and to a pronounced lowering of the efficiency with which an electron can move from the reduced intersystem electron acceptors to the PSI end acceptors (δ_Ro). Stomatal conductance was affected by both treatments. Biomass was found to be affected by O₃ fumigation (for 30 days), decreasing by 40% at 80 ppb and by more than 70% under 120 ppb. Our findings indicate that biomass decline is due both to the lowering of CCI and the lowering of photosynthetic efficiency parameters. They thus suggest that two simple, non-invasive and rapid methods, namely, the analysis of OJIP fluorescence transients and the measurement of CCI, can be used to screen the effect of elevated O₃ on biomass of canola plants.

https://ift.tt/2tHaKsp

Testing a priming account of the contingent-capture effect

Abstract

In the contingent-capture protocol, singleton cues that have a target's searched-for feature capture attention, but cues that do not have the target's searched-for feature do not, a result labeled the contingent-capture effect. The contingent-capture effect is usually regarded as evidence for the observers' ability to establish search settings for certain nonspatial features in a top-down manner. However, in recent years it has become increasingly clear that selection history is also a powerful mediator of attentional capture. In this vein, it has been suggested that contingent-capture effects could emerge as a result of (intertrial) priming: The idea is that features that have been encountered previously in the target are primed, so that cues that have these features automatically capture attention in a subsequent encounter. Here we tested a strong version of the priming account of the contingent-capture effect. We wanted to know whether cues that had target features would capture attention when the corresponding features were not part of the instructions (i.e., when the corresponding features were task-irrelevant). The results suggested that a strong version of the priming account of contingent capture is not supported. In five experiments, we found little evidence that the contingent-capture effect could be explained by (intertrial) priming of task-irrelevant features alone. These results show that processes beyond priming through task-irrelevant features are critical for contingent-capture effects.

https://ift.tt/2UeZRJQ

Dorsal Augmentation with Diced Conchal Cartilage Wrapped in Retroauricular Fascia

Abstract

Background

Dorsal augmentation is of primary importance to shape an ideal nose. Although costal cartilage is still used for this purpose, diced cartilage grafts wrapped in autogenous fascia became more and more popular in recent decades. In this paper, the authors report their experience with a new combination made by diced conchal cartilage wrapped in retroauricular fascia in primary and secondary cases.

Methods

The clinical records of the first 19 patients to undergo dorsal augmentation with this technique were reviewed. The entire concha has been harvested and, once diced, wrapped in a sleeve of retroauricular fascia obtained using the same incision. Quilting reabsorbable sutures closed the mastoid dead space and prevented the risk of hematoma. The graft has been used in all the cases through a closed approach.

Conclusion

The use of diced cartilage is nowadays considered one of the best options among the available procedures for dorsal augmentation. Diced conchal cartilage wrapped in posterior auricular fascial graft is a new, simple and safe procedure that eliminates the necessity of a secondary donor site (temple or thorax), speeds up the operation and leaves a well-concealed scar behind the ear. Its main disadvantages toward costal diced cartilage wrapped in rectus abdominis fascia are the minor quantity of cartilage that can be obtained, even in case of bilateral harvest, and compared to temporal fascia a longer postoperative swelling (6–8 weeks).

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

https://ift.tt/2T6mEv2

Miktoarm star polymers nanocarrier: synthesis, characterisation, and in-vitro drug release study

Abstract

Conjugation of poly(ethylene glycol) (PEG) to poly(lactide-co-glycolide) (PLGA) renders the latter with enhanced biocompatibility and broader overall capability in biomedical application. Novel miktoarm star polymers comprising PLGA and PEG segments are of interest for their potential as drug carriers. Thus, a series of miktoarm star copolymers, PLGA-(mPEG)₂, with different PLGA arm molecular weights and methoxy-PEG (mPEG) arm (2000 g/mol), were synthesised via a four-step reaction using carbodiimide chemistry with a low steric hindrance trifunctional linker aminoadipic acid (AAA) and characterised by proton nuclear magnetic resonance (¹H NMR), fourier transform infrared (FTIR), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). Results show that the miktoarm star polymers PLGA_17.0-AAA(mPEG)₂ and PLGA_43.4-AAA(mPEG)₂ formed stable nanoparticles and PLGA_4.6-AAA(mPEG)₂ self-assembled into stable nanomicelles. Fluorescence spectroscopy showed that the critical micelle concentration of PLGA_4.6-AAA(mPEG)₂ was very low at 6.03 × 10⁻⁷ g/mL. Model drug ibuprofen encapsulated nanoparticles and nanomicelles had good drug loading, high encapsulation efficiency, narrow size distribution, and spherical morphology with negative surface charges. The mean particle size increased with increasing PLGA molecular weights, from 37.28 ± 1.03 to 151.5 ± 0.86 nm. In-vitro release of model drug ibuprofen over 7 days from PLGA_43.4-AAA(mPEG)₂ nanoparticles (61.65 ± 3.04%) was higher than those of PLGA_4.6-AAA(mPEG)₂ nanomicelles (26.93 ± 1.49%) and PLGA_17.0-AAA(mPEG)₂ nanoparticles (10.57 ± 0.29%), with all demonstrating controlled release characteristics. In conclusion, the novel miktoarm star polymers PLGA_43.4-AAA(mPEG)₂ and PLGA_17.0-AAA(mPEG)₂ and their nanoparticles, and PLGA_4.6-AAA(mPEG)₂ and its nanomicelles have a great potential as a nanocarrier for controlled delivery of hydrophobic drugs.

https://ift.tt/2SyfgU7

Draft Genome of Burkholderia cenocepacia TAtl-371, a Strain from the Burkholderia cepacia Complex Retains Antagonism in Different Carbon and Nitrogen Sources

Abstract

Burkholderia cenocepacia TAtl-371 was isolated from the rhizosphere of a tomato plant growing in Atlatlahucan, Morelos, Mexico. This strain exhibited a broad antimicrobial spectrum against bacteria, yeast, and fungi. Here, we report and describe the improved, high-quality permanent draft genome of B. cenocepacia TAtl-371, which was sequenced using a combination of PacBio RS and PacBio RS II sequencing methods. The 7,496,106 bp genome of the TAtl-371 strain is arranged in three scaffolds, contains 6722 protein-coding genes, and 99 RNA only-encoding genes. Genome analysis revealed genes related to biosynthesis of antimicrobials such as non-ribosomal peptides, siderophores, chitinases, and bacteriocins. Moreover, analysis of bacterial growth on different carbon and nitrogen sources shows that the strain retains its antimicrobial ability.

https://ift.tt/2EjCXdS

Effects of Cigarette Smoke on Fat Graft Survival in an Experimental Rat Model

Abstract

Introduction

A fat graft is the closest thing to being the ideal soft tissue filler. Although it has many advantages, reliability of late-term survival is a never-ending debate. Although there are observational studies that research the effect of cigarette smoke on fat graft take in clinical setting, there has not been an objective experimental animal study on the affect of smoking on fat graft survival. The aim of our study is to search if smoking has an affect on fat grafts.

Materials and Methods

Twenty-two Sprague-Dawley type rats were used. Exposure was maintained via a passive smoke exposure system. Rats were divided into three groups regarding their exposure period. At the end of the study, transferred fat grafts were extracted and weighed with a precision scale, an arterial blood sample was taken for biochemical analysis, and grafts were sent to the pathology laboratory for immunohistochemical assessment.

Results

There were meaningful differences between the control group and the other two groups in graft weight loss, serum cotinine, tissue MDA, adipose tissue/fibrosis ratio, stem cell counts, perilipin positive cell density and inflammation density. Furthermore, we detected meaningful correlations between serum cotinine, tissue MDA and graft weight loss.

Conclusion

Fat graft takes with the same mechanisms as a wound heals. So like wound healing, cigarette smoke has a negative affect on fat graft survival. A fat graft is by its nature an elective procedure so to improve our late-term success, cigarette smoke exposure should be kept to a minimum for increased reliability.

No Level Assigned

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

https://ift.tt/2Xqv2Ea

Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2

Abstract

Objective

L-type amino acid transporter 1 (LAT1) is strongly expressed on the cell membrane in various types of human cancer cells, while being minimally expressed in normal or inflammatory tissues. Therefore, LAT1-targeting PET tracers have been developed for cancer-specific imaging. The purpose of this study was to study the distribution of two LAT1-targeting PET tracers, L-4-borono-2-¹⁸F-fluoro-phenylalanine (¹⁸F-FBPA) and L-3-¹⁸F-alpha-methyl tyrosine (¹⁸F-FAMT), in relation to the tumor blood flow, using rat xenograft models.

Methods

Rat tumor xenograft models of C6 glioma (n = 4; tumors = 8) and MIA PaCa-2 (pancreatic cancer) (n = 4; tumors = 6) were used. The expressions of LAT1 and CD98hc were evaluated by both immunofluorescence staining and western blot analysis. Dynamic PET was performed after injection of ¹⁸F-FAMT or ¹⁸F-FBPA (scan duration = 70 min) following ¹⁵O-water PET (scan duration = 10 min). The PET data were subjected to kinetic analyses, and the K₁, k₂, and total distribution volume (V_t) were calculated using the one-tissue compartment model. The accumulation of the LAT1 tracers was expressed in terms of their V_t. Tumor blood flow (TBF) was represented by the K₁ value in ¹⁵O-water PET.

Results

LAT1/CD98hc expression was confirmed in both xenografts by immunofluorescence staining. Western blot analysis showed higher functional expression of LAT1 in the C6 glioma cells as compared to the MIA PaCa-2 cells (C6 glioma/MIA PaCa-2 relative expression ratio = 1.70). The V_t values of both ¹⁸F-FBPA and ¹⁸F-FAMT were significantly higher in the C6 glioma xenografts than in the MIA PaCa-2 xenografts (C6 glioma: 2.27 ± 0.35 and 2.03 ± 0.23, respectively; MIA PaCa-2: 1.28 ± 0.26 and 1.35 ± 0.15, respectively). Meanwhile, there was no significant correlation of the V_t value of either ¹⁸F-FBPA or ¹⁸F-FAMT with the TBF, in either the C6 glioma or the MIA PaCa-2 xenografts.

Conclusions

This study revealed that total distribution volumes of the LAT1-targeting PET tracers ¹⁸F-FBPA and ¹⁸F-FAMT were independent of the tumor blood flow and might reflect the functional expression levels of LAT1 in the C6 glioma and MIA PaCa-2 xenograft models.

https://ift.tt/2GQeZuk

Intracerebroventricular Delivery of Recombinant NAMPT Deters Inflammation and Protects Against Cerebral Ischemia

Abstract

Our previous study indicated that nicotinamide phosphoribosyltransferase (NAMPT) is released from cells and might be an important extracellular neuroprotective factor in brain ischemia. Here, we tested whether NAMPT protects against ischemic brain injury when administered directly into the intracerebroventricular (ICV) compartment of the cranium. Recombinant NAMPT protein (2 μg) was delivered ICV in mice subjected to 45-min middle cerebral artery occlusion (MCAO), and the effects on infarct volume, sensorimotor function, microglia/macrophage polarization, neutrophil infiltration, and BBB integrity were analyzed. The results indicate that ICV administration of NAMPT significantly reduced infarct volume, retained its beneficial properties even when ICV administration was delayed by 6 h after MCAO, and improved neurological outcomes. NAMPT treatment inhibited pro-inflammatory microglia/macrophages, promoted microglia/macrophage polarization toward the anti-inflammatory phenotype, and reduced the infiltration of neutrophils into the perilesional area after brain ischemia. In vitro studies indicated that multiple pro-inflammatory microglial markers/cytokines were downregulated while multiple anti-inflammatory microglial markers/cytokines were induced in primary microglial cultures treated with NAMPT protein. NAMPT treatment also fortified the blood–brain barrier (BBB), as shown by reduced extravascular leakage of the small-molecule tracer Alexa Fluor 555 Cadaverine and larger-sized endogenous IgGs into brain parenchyma. Thus, NAMPT may protect against ischemic brain injury partly through a novel anti-inflammatory mechanism, which in turn maintains BBB integrity and reduces the infiltration of peripheral inflammatory cells. Taken together, these results provide validation of recombinant NAMPT delivery into the extracellular space as a potential neuroprotective strategy for stroke.

https://ift.tt/2VxSAp5

Assessing the Metabolomic Profile of Multiple Sclerosis Patients Treated with Interferon Beta 1a by 1 H-NMR Spectroscopy

Abstract

Metabolomic research has emerged as a promising approach to identify potential biomarkers in multiple sclerosis (MS). The aim of the present study was to determine the effect of interferon beta (IFN ß) on the metabolome of MS patients to explore possible biomarkers of disease activity and therapeutic response. Twenty-one MS patients starting IFN ß therapy (Rebif® 44 μg; s.c. 3 times per week) were enrolled. Blood samples were obtained at baseline and after 6, 12, and 24 months of IFN ß treatment and were analyzed by high-resolution nuclear magnetic resonance spectroscopy. Changes in metabolites were analyzed. After IFN ß exposure, patients  were divided into responders and nonresponders according to the "no evidence of disease activity" (NEDA-3) definition (absence of relapses, disability progression, and magnetic resonance imaging activity), and samples obtained at baseline were analyzed to evaluate the presence of metabolic differences predictive of IFN ß response. The results of the investigation demonstrated differential distribution of baseline samples compared to those obtained during IFN ß exposure, particularly after 24 months of treatment (R²X = 0.812, R²Y = 0.797, Q² = 0.613, p = 0.003). In addition, differences in the baseline metabolome between responder and nonresponder patients with respect to lactate, acetone, 3-OH-butyrate, tryptophan, citrate, lysine, and glucose levels were found (R²X = 0.442, R²Y = 0.768, Q² = 0.532, p = 0.01). In conclusion, a metabolomic approach appears to be a promising, noninvasive tool that could potentially contribute to predicting the efficacy of MS therapies.

https://ift.tt/2H9rgZZ

Real-time iris segmentation and its implementation on FPGA

Abstract

This paper presents a real-time iris segmentation technique that is well suited to a fast implementation on an FPGA. One major hurdle associated with iris segmentation techniques is the use of iterative processes that lead to expensive hardware implementations. To circumvent this, the proposed algorithm uses the sign image obtained from subtracting the background, along with morphological operators to localise the pupil. The outer boundary is located by first normalising a selected image region that contains the iris, and then using a first-order gradient operator. The proposed non-iterative algorithm is implemented on an FPGA. Four near infrared (NIR) iris public databases, namely: CASIA-IrisV3-Lamp, MMU v1.0, ND-IRIS-0405 and NIST ICE 2005, are used to test the proposed algorithm. The proposed method for iris segmentation and normalization gives much better accuracy than the existing state-of-the-art methods implemented on hardware. The proposed realisation requires about 45% fewer logic registers and 52% fewer logic elements than the existing state-of-the-art implementations.

https://ift.tt/2IHBuTZ

Correction to: The usability of climate information in sub-national planning in India, Kenya and Uganda: the role of social learning and intermediary organisations

The article was published without the Reference section.

https://ift.tt/2Tagk5F

Univariate comparison of PRx, PAx, and RAC—much ado about what?

https://ift.tt/2XrMPLa

Preparation, characterization, and reaction kinetics of poly (lactic acid)/amidated graphene oxide nanocomposites based on reactive extrusion process

Abstract

The poly (lactic acid) (PLA)/amidated graphene oxide (AGO) nanocomposites were prepared by reactive extrusion process with L-lactide as raw material, zinc lactate as catalyst, hexamethylene diisocyanate as chain extender, and AGO as nano-nucleating agent prepared by amidation. The molecular weight of PLA and PLA/AGO were 29,424 g/mol and 32,516 g/mol, respectively, under the optimum conditions, which were obtained through orthogonal experiments. The structure and performance of PLA and PLA/AGO nanocomposites were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscope (TEM), mechanical properties, differential scanning calorimetry (DSC), Thermogravimetric analysis (TGA), and capillary rheology. The results showed that the AGO could uniformly dispersed in PLA matrix, which significantly improved the mechanical properties, crystallinity, and thermal stability of PLA. Kinetics studies showed that the polymerization reaction model presented the second-order reaction, and the apparent rate constant of PLA/AGO nanocomposites was 7.612 × 10³ g·mol ⁻¹ ·min ⁻¹.

https://ift.tt/2NxCrNh

Statin use after diagnosis is associated with an increased survival in esophageal cancer patients: a Belgian population-based study

Abstract

Purpose

Preclinical studies have shown that statins reduce proliferation in esophageal cancer. Three recent observational studies have shown encouraging results but suffered from limitations. This work aimed to assess at the Belgian population level whether statin usage was associated with a decreased mortality in esophageal cancer patients.

Methods

We conducted an observational, population-based study by linking data of the Belgian Cancer Registry (BCR) with medical claims data coming from health insurance companies and mortality records collected by regional governments for patients diagnosed with esophageal cancer between 2004 and 2014. Using time-dependent Cox regression models, hazard ratios (HRs) and 95% confidence intervals (CI) for overall and cancer-specific mortality were calculated.

Results

Of 6,238 patients with stage I-III esophageal cancer, post-diagnostic use of statins was found in 1,628 (26%) patients. Statins use after diagnosis was associated with a reduction in overall mortality (adjusted HR = 0.84, 95% CI [0.77; 0.92]) and cancer-specific mortality (adjusted HR = 0.87, 95% CI [0.78; 0.97]). Similar association were also seen for pre-diagnostic statin use in overall (adjusted HR = 0.83, 95% CI [0.76–0.91]) and cancer-specific analysis (adjusted HR = 0.86, 95% CI [0.77–0.96]).

Conclusions

In this large cohort of Belgian patients with esophageal cancer, statins use after diagnosis was associated with a decreased mortality.

https://ift.tt/2UdDiFp

Merkel Cell Carcinoma: Therapeutic Update and Emerging Therapies

Abstract

Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine skin cancer whose incidence has almost doubled in recent decades. Risk factors for MCC include age > 65 years, immunosuppression, sun exposure and infection by Merkel cell polyomavirus. MCC usually presents as rapidly growing, firm, red to violaceous nodule localized on the sun-exposed skin. Surgery followed by radiation therapy is considered to be the first-line treatment for primary or loco-regional MCC in order to prevent recurrences and lymph node metastasis, while chemotherapy has always been used to treat advanced forms. However, responses to chemotherapy are mostly of short duration, and the associated clinical benefit on overall survival is still unclear. The use of checkpoint inhibitors (CPIs) has shown good results in the treatment of advanced MCC and, consequently, CPIs are considered emerging immunotherapeutic options for these patients, although there are still no standardized treatments for patients with metastatic disease. Here we present a complete overview of the different possibilities for the treatment of MCC according to the stage of the disease, focusing on the emerging immunotherapies used for treating advanced MCC.

https://ift.tt/2XuD6Uz

Celastrol suppresses experimental autoimmune encephalomyelitis via MAPK/SGK1-regulated mediators of autoimmune pathology

Abstract

Objective and design

Multiple sclerosis (MS) is a debilitating autoimmune disease involving immune dysregulation of the pathogenic T helper 17 (Th17) versus protective T regulatory (Treg) cell subsets, besides other cellular aberrations. Studies on the mechanisms underlying these changes have unraveled the involvement of mitogen-activated protein kinase (MAPK) pathway in the disease process. We describe here a gene expression- and bioinformatics-based study showing that celastrol, a natural triterpenoid, acting via MAPK pathway regulates the downstream genes encoding serum/glucocorticoid regulated kinase 1 (SGK1), which plays a vital role in Th17/Treg differentiation, and brain-derived neurotrophic factor (BDNF), which is a neurotrophic factor, thereby offering protection against experimental autoimmune encephalomyelitis (EAE) in mice.

Methods

We first tested the gene expression profile of splenocytes of EAE mice in response to the disease-related antigen, myelin oligodendrocyte glycoprotein (MOG), and then examined the effect of celastrol on that profile.

Results

Interestingly, celastrol reversed the expression of many MOG-induced genes involved in inflammation and immune pathology. The MAPK pathway involving p38MAPK and ERK was identified as one of the mediators of celastrol action. It involved suppression of SGK1 but upregulation of BDNF, which then contributed to protection against EAE.

Conclusion

Our results not only provide novel insights into disease pathogenesis, but also offer promising therapeutic targets for MS.

https://ift.tt/2Hdqgo3

Increased risk of tuberculosis in oral cancer patients in an endemic area: a nationwide population-based study

Abstract

Objectives

We investigated the incidence of tuberculosis (TB) in patients with newly diagnosed oral cancer and analyzed the risk factors for TB development and mortality in oral cancer patients.

Materials and methods

We used Taiwan's National Health Insurance Database to determine the incidence of TB and to analyze the risk factors for TB in patients newly diagnosed with oral cancer. From 2000 to 2011, we identified 40,327 oral cancer patients and the same number of subjects from the general population matched for sex, age, and comorbidities at a 1:1 ratio.

Results

Compared with the matched cohort, oral cancer patients exhibited a higher risk for TB (adjusted hazard ratio (aHR) 2.36, 95% confidence interval (CI) 2.06–2.71). Age ≥ 50 (aHR 1.90, 95% CI 1.57–2.29), being male (aHR 1.98, 95% CI 1.36–2.89), having diabetes mellitus (aHR 1.31, 95% CI 1.05–1.64), alcohol use disorder (aHR 1.42, 95% CI 1.06–1.89), human immunodeficiency virus (HIV) (aHR 8.24, 95% CI 2.05–33.14), chemotherapy (aHR 1.41, 95% CI 1.15–1.72), and radiotherapy for oral cancer (aHR 1.92, 95% CI 1.57–2.36) were identified as independent risk factors for TB in oral cancer patients. Hyperlipidemia was an independent protective factor for TB in oral cancer patients.

Conclusion

Old age, male sex, diabetes mellitus, alcohol use disorder, and HIV were independent risk factors for TB in patients with oral cancer.

Clinical relevance

High-risk oral cancer patients should be regularly screened for TB, especially those in endemic areas.

https://ift.tt/2EnbHuX

A Vesicular Stomatitis Virus-Based Vaccine Carrying Zika Virus Capsid Protein Protects Mice from Viral Infection

https://ift.tt/2BRknt5

Haptoglobin 2-2 Genotype is Associated with More Advanced Disease in Subjects with Non-Alcoholic Steatohepatitis: A Retrospective Study

Abstract

Introduction

Haptoglobin (Hp) genotypes were reported as an independent risk factor for metabolic diseases. This study aimed to investigate the association between Hp gene polymorphism and the severity of nonalcoholic fatty liver disease (NAFLD).

Methods

A total of 441 subjects (NAFLD group, n = 272; healthy control, n = 169) were recruited, and their clinical biochemical parameters were measured in all subjects. Haptoglobin genotyping was performed using genomic DNA extracted from peripheral blood leukocytes. Among the NAFLD group, 107 patients underwent liver biopsy, and histology was evaluated by a pathologist on the basis of the CRN scoring system.

Results

NAFLD patients had much lower frequency of Hp 1-1 genotype and higher frequency of Hp 2-2 than healthy controls (0.4% vs 9.5%, 55.8% vs 47.9%, P < 0.001). NAFLD patients with Hp 2-2 genotype had much higher levels of body mass index (BMI), total cholesterol (TC), liver enzymes, ferritin, and controlled attenuation parameter (CAP) values than non-Hp 2-2 genotype (P < 0.05). In histology, patients with nonalcoholic steatohepatitis (NASH) had higher frequency of Hp 2-2 genotype than non-NASH patients (71.3% vs 22.2%, P < 0.001); patients with significant fibrosis had higher frequency of Hp 2-2 genotype (78.3% vs 54.8%, P < 0.05) than no/mild fibrosis patients. NAFLD patients with Hp 2-2 genotype had higher proportion with higher steatosis scores, lobular inflammation scores, ballooning scores, NAFLD activity scores (NAS), and fibrosis stages (P < 0.05 for all) than Hp 2-2 groups. Furthermore, Hp 2-2 genotype was independently associated with NASH (OR = 5.985, P < 0.05) and significant fibrosis (OR = 6.584, P < 0.05).

Conclusions

Hp 2-2 genotype is closely associated with the severity of NAFLD.

https://ift.tt/2TkO93b

Case Series of Combined iStent Implantation and Phacoemulsification in Eyes with Primary Angle Closure Disease: One-Year Outcomes

Abstract

Purpose

To evaluate the safety and efficacy of combined iStent® trabecular micro-bypass device (Glaukos, Laguna Hills, CA) and phacoemulsification in eyes with primary angle closure disease.

Methods

A two-center prospective interventional case series of consecutive patients with primary angle closure (PAC) or primary angle closure glaucoma (PACG) on at least one glaucoma medication, who underwent iStent implantation with cataract surgery. Postoperatively, patients were assessed on days 1 and 7, and months 1, 3, 6, and 12. The intraocular pressure (IOP), glaucoma medication use, visual acuity, and the presence of complications were assessed at each visit. Complete success was defined as IOP reduction of at least 20% without the use of glaucoma medications.

Results

Thirty-seven eyes with angle closure disease were included in this study. At 1-year, postoperative mean IOP (14.8 ± 3.94 mmHg) was significantly decreased compared with preoperative medicated (17.5 ± 3.82 mmHg, p = 0.008) and unmedicated (24.6 ± 3.41 mmHg, p < 0.001) IOP. Complete success was achieved in 89.2% of the eyes. The number of glaucoma medications decreased from 1.49 ± 0.77 to 0.14 ± 0.48 (p < 0.001). Preoperative medicated IOP was a risk factor for failure (hazard ratio 3.45, 95% confidence interval 1.52–7.85, p = 0.003), after adjustment for age, gender, and race. The most common postoperative complications were iStent occlusion with iris (27.0%) and hyphema (18.9%). There were no sight-threatening intraoperative or postoperative complications.

Conclusion

Combined iStent implantation with cataract surgery was effective in lowering the IOP and the number of glaucoma medications for at least 12 months, with a favorable safety profile.

Funding

Glaukos Corporation; NMRC Science Translational and Applied Research (STAR) award.

https://ift.tt/2IKp7qe

Medical specialty visits and diagnoses received by Saudi patients prior to a diagnosis of narcolepsy

Abstract

Purpose

Narcolepsy is an uncommon neurological disorder characterized by excessive daytime sleepiness (EDS) and multiple other symptoms. Due to the under-recognition of narcolepsy symptoms, patients are often misdiagnosed. This study aimed to assess the types of specialties visited and the diagnoses received by Saudi patients prior to their narcolepsy diagnosis.

Methods

The study included 55 consecutive patients with type-1 and type-2 narcolepsy who attended the narcolepsy clinic between August 2017 and December 2017. Narcolepsy was diagnosed according to the International Classification of Sleep Disorders–third edition criteria. We evaluated sociodemographic data, the specialties visited, and diagnoses and treatments received prior to visiting a sleep specialist.

Results

The mean diagnostic delay was 9.1 ± 8.4 years (1–43 years). Multiple linear regression analysis identified early onset as the only predictor of a delayed diagnosis (β coefficient = − 0.262, p = 0.03). EDS was the main symptom that prompted patients to seek medical consultation, and only one patient had been (1.8%) referred with the diagnosis of narcolepsy. In the study group, 82% of the patients were misdiagnosed with a mental or neurological disorder or were thought to be afflicted by "envy," "evil eye," or "black magic" before receiving a correct diagnosis. No significant differences were detected between patients with narcolepsy type-1 and narcolepsy type-2.

Conclusions

Delays in diagnosing narcolepsy remain a major problem for Saudi patients with this disorder. We found that Saudi patients with narcolepsy had visited several medical specialists and faith healers and were misdiagnosed prior to visiting a sleep specialist.

https://ift.tt/2EhLU7d

Factors Associated with Employer Support for Injured Workers During a Workers’ Compensation Claim

Abstract

Purpose The employer/worker relationship can be an important catalyst for—or obstacle to—successful return to work (RTW). An understanding of factors associated with an injured worker's relationship with their employer, and employer involvement in RTW planning, is warranted. Methods Analysis of n = 8808 cross-sectional survey responses from injured workers in nine Australian workers' compensation (WC) jurisdictions. Workers completed a telephone survey between 6 and 24 months post-WC claim acceptance. Factors associated with the worker's perception of employer support were examined using ordinal regression. Factors associated with employer provision of RTW plans were examined using logistic regression. Results Factors associated with employer support included being aged over 50 years, not having a mental health condition, better self-rated health and less time between injury and claim. Factors associated with having a RTW plan included being female, not having a mental health condition and working for a self-insurer. Factors associated with having a written RTW plan included being female and being under 50 years. There was wide variation in the provision of RTW plans between WC jurisdictions. Conclusions There are strong associations between worker, claim and injury-related factors and the injured worker's experience of employer support. Identification of workers at risk of receiving inadequate support during the RTW process may enable interventions to improve support and RTW outcomes.

https://ift.tt/2NAMu49

Risk of exposure of a selected rural population in South Poland to allergenic mites. Part I: indoor acarofauna of one-family houses

Abstract

The aim of this study was to investigate the occurrence of mites in dust samples from houses in agricultural areas of South Poland, with particular reference to allergenic and parasitic species as a potential risk factor of diseases among people. A total of 250 dust samples from 50 single-family houses situated in Stryszawa and vicinity (Małopolskie province) were examined for the presence of domestic mites. Dust was taken from beds, floors in bedrooms, upholstery furniture, floors in family rooms and from floors in kitchens. Mites were found in 74.8% of samples collected. A total of 5340 mite specimens were isolated, including 2771 members of the family Pyroglyphidae (51.9%). Dominants were Dermatophagoides pteronyssinus (36.4% of all mites) and Gohieria fusca (25.1%), followed by Chortoglyphus arcuatus (18.3%) and D. farinae (15.1%). Dermatophagoides pteronyssinus was also the most frequent species (53.2% of the total count of samples examined), followed by G. fusca (42.4%), D. farinae (37.2%) and C. arcuatus (36.4%). Lepidoglyphus destructor was found more frequently than Glycyphagus domesticus in the examined samples. Density of D. pteronyssinus was associated with beds, presence of pets, coal stoves used for heating, lower number of rooms, higher cooking frequency, higher washing frequency, working housewife, open kitchen, wooden floors in kitchens, lower cleaning frequency, type of upholstery furniture in living rooms (arm chairs), lower humidity and higher temperature.

https://ift.tt/2H90twT

IT development in radiology - an ESR update on the Digital Imaging Adoption Model (DIAM)

Abstract

The Digital Imaging Adoption Model (DIAM), a joint project established in 2016 by the European Society of Radiology (ESR) and the Healthcare Information and Management Systems Society (HIMSS), is designed to assist imaging institutions in implementing increasingly integrated IT systems and improving patient care. The model provides a framework through which existing capacities can be assessed and strategy for future institutional development elaborated. DIAM has already been adopted by 58 leading institutions in 18 countries. This article will first provide an overview of the DIAM framework; subsequently, it will consider what its adoption has revealed so far, both through the analysis of global data and through specific case studies; finally, it will outline the future potential and goals of the project.

https://ift.tt/2Vsyr3C

Handover of anesthesia care is associated with an increased risk of delirium in elderly after major noncardiac surgery: results of a secondary analysis

Abstract

In patients undergoing major surgery, complete handover of intraoperative anesthesia care is associated with adverse postoperative outcomes including high mortality and more major complications. The purpose of this study was to explore the association between the intraoperative complete handover between anesthesiologists and the occurrence of postoperative delirium. This was a secondary analysis of the database of a previously published clinical trial. Seven hundred patients aged 65 years or older, who were admitted to the intensive care unit after noncardiac surgery, were included. Delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the first 7 postoperative days. Other postoperative outcomes were also monitored. The association between the intraoperative complete handover of anesthesia care and the development of postoperative delirium was analyzed with a logistic regression model. Of the 700 enrolled patients, 111 (15.9%) developed postoperative delirium within 7 days. After correction for confounding factors, intraoperative complete handover between anesthesiologists was associated with an increased risk of postoperative delirium (OR 1.787, 95% CI 1.012–3.155, P = 0.046). Patients with intraoperative complete handover also had higher incidence of non-delirium complications (P = 0.003) and stayed longer in hospital after surgery (P = 0.002). For elderly patients admitted to the intensive care unit after noncardiac surgery, intraoperative complete handover of anesthesia care was associated with an increased risk of postoperative delirium. Chinese Clinical Trial Registry (http://www.chictr.org.cn): ChiCTR-TRC-10000802.

https://ift.tt/2H9TaoP

Prognostic ability of the German version of the STarT Back tool: analysis of 12-month follow-up data from a randomized controlled trial

Abstract

Background

Stratified care is an up-to-date treatment approach suggested for patients with back pain in several guidelines. A comprehensively studied stratification instrument is the STarT Back Tool (SBT). It was developed to stratify patients with back pain into three subgroups, according to their risk of persistent disabling symptoms. The primary aim was to analyse the disability differences in patients with back pain 12 months after inclusion according to the subgroups determined at baseline using the German version of the SBT (STarT-G). Moreover, the potential to improve prognosis for disability by adding further predictor variables, an analysis for differences in pain intensity according to the STarT-Classification, and discriminative ability were investigated.

Methods

Data from the control group of a randomized controlled trial were analysed. Trial participants were members of a private medical insurance with a minimum age of 18 and indicated as having persistent back pain. Measurements were made for the risk of back pain chronification using the STarT-G, disability (as primary outcome) and back pain intensity with the Chronic Pain Grade Scale (CPGS), health-related quality of life with the SF-12, psychological distress with the Patient Health Questionnaire-4 (PHQ-4) and physical activity. Analysis of variance (ANOVA), multiple linear regression, and area under the curve (AUC) analysis were conducted.

Results

The mean age of the 294 participants was 53.5 (SD 8.7) years, and 38% were female. The ANOVA for disability and pain showed significant differences (p < 0.01) among the risk groups at 12 months. Post hoc Tukey tests revealed significant differences among all three risk groups for every comparison for both outcomes. AUC for STarT-G's ability to discriminate reference standard 'cases' for chronic pain status at 12 months was 0.79. A prognostic model including the STarT-Classification, the variables global health, and disability at baseline explained 45% of the variance in disability at 12 months.

Conclusions

Disability differences in patients with back pain after a period of 12 months are in accordance with the subgroups determined using the STarT-G at baseline. Results should be confirmed in a study developed with the primary aim to investigate those differences.

https://ift.tt/2tGX4xu

Präparatequalität nach laparoskopischer vs. offener Rektumkarzinomchirurgie

https://ift.tt/2StlGnv

Real-World Treatment Patterns Among Patients Initiating Small Molecule Kinase Inhibitor Therapies for Thyroid Cancer in the United States

Abstract

Introduction

Little is known about real-world use of small molecule kinase inhibitors (SMKI) for advanced thyroid cancer in the United States. This study examined prescribing patterns of SMKI agents recommended by the National Comprehensive Cancer Center (NCCN).

Methods

This retrospective study used a national health insurance database to identify patients diagnosed with thyroid cancer during 1/1/2006–6/30/2016 and with prescription claims for NCCN-recommended SMKI during 1/1/2010–5/31/2016 whose first claim date was the index date. Inclusion also required continuous enrollment in a health plan for 3 months pre-index (baseline) and ≥ 1 month post-index (follow-up) with no claims for SMKI during baseline. Lines of therapy (LOT) were defined by the date of SMKI claims and days of drug supply. Median time to SMKI discontinuation in each LOT was estimated by Kaplan–Meier method.

Results

The study included 217 patients. During follow-up (mean duration 499.0 days), 35.5% of patients (n = 77) received a second or later LOT; among patients with ≥ 12 months follow-up after first LOT (LOT1) initiation, 53.1% (n = 60) received a second or later LOT. Median treatment duration was 5.0 months for LOT1 and 5.1 months for LOT2. Over the entire follow-up period (2010–2016), sorafenib was the most common regimen in LOT1 (36.9% of patients) and LOT2 (24.7%) followed by sunitinib and levantinib (13.4% each) in LOT1 and sunitinib (19.5%) in LOT2. Starting in 2015, the year lenvatinib was approved for differentiated thyroid cancer, lenvatinib was the most common first-line regimen among patients initiating LOT1 in 2015 (43.4%) and 2016 (66.7%).

Conclusion

Sorafenib was the most common first-line agent during 2010–2014 but was supplanted by lenvatinib starting in 2015. Approximately 36–53% of patients received a second-line treatment. Median treatment duration results suggested potential benefit of SMKI in second-line therapy. SMKI treatment after first-line failure may be considered for appropriately selected patients.

Funding

Eisai, Inc. (Woodcliff Lake, NJ).

https://ift.tt/2ECxjEZ

Two-site regional oxygen saturation and capnography monitoring during resuscitation after cardiac arrest in a swine pediatric ventricular fibrillatory arrest model

Abstarct

To investigate the use of two-site regional oxygen saturations (rSO₂) and end tidal carbon dioxide (EtCO₂) to assess the effectiveness of resuscitation and return of spontaneous circulation (ROSC). Eight mechanically ventilated juvenile swine underwent 28 ventricular fibrillatory arrests with open cardiac massage. Cardiac massage was administered to achieve target pulmonary blood flow (PBF) as a percentage of pre-cardiac arrest baseline. Non-invasive data, including, EtCO₂, cerebral rSO₂ (C-rSO₂) and renal rSO₂ (R-rSO₂) were collected continuously. Our data demonstrate the ability to measure both rSO₂ and EtCO₂ during CPR and after ROSC. During resuscitation EtCO₂ had a strong correlation with goal CO with r = 0.83 (p < 0.001) 95% CI [0.67–0.92]. Both C-rSO₂ and R-rSO₂ had moderate and statistically significant correlation with CO with r = 0.52 (p = 0.003) 95% CI (0.19–0.74) and 0.50 (p = 0.004) 95% CI [0.16–0.73]. The AUCs for sudden increase of EtCO₂, C-rSO₂, and R-rSO₂ at ROSC were 0.86 [95% CI, 0.77–0.94], 0.87 [95% CI, 0.8–0.94], and 0.98 [95% CI, 0.96–1.00] respectively. Measurement of continuous EtCO₂ and rSO₂ may be used during CPR to ensure effective chest compressions. Moreover, both rSO₂ and EtCO₂ may be used to detect ROSC in a swine pediatric ventricular fibrillatory arrest model.

https://ift.tt/2XwXLHg

Bone Metabolism in Adolescents and Adults Undergoing Roux-En-Y Gastric Bypass: a Comparative Study

Abstract

Objective

To compare the bone metabolism of adolescents and adults with obesity before undergoing a Roux-en-Y gastric bypass (RYGB) and 6 and 12 months after the surgery.

Materials and Methods

Adolescents (G1) and adults (G2) with obesity assessed before (T0), six (T1), and 12 months after (T2) RYGB. Sun exposure, serum concentrations of 25(OH)D, calcium, phosphorous, magnesium, zinc, alkaline phosphatase, parathyroid hormone (PTH), and bone mineral density (BMD) were evaluated.

Results

Sixty adolescents and 60 adults were assessed. At T0, there was no significant difference between the groups' serum 25(OH)D levels (G1 21.87 + 7.52 ng/mL, G2 21.73 + 7.60 ng/mL, p = 0.94) or sun exposure (G1 17 ± 2.0 min/day, G2 13.2 ± 5.2 min/day, p = 0.85). G1 had high levels of inadequacy of calcium (66.7%), phosphorous (80.0%), and zinc (18.3%) at T0 and had a significant fall in their 25(OH)D (p < 0.01) and magnesium (p < 0.01) levels from T1 to T2. G2 saw a significant lowering of their serum zinc levels from T0 to T1 and T2 (T1 p < 0.01; T2 p < 0.01). In both groups, there was a significant rise in PTH from T1 to T2 (G1 p = 0.04, G2 p = 0.02) and from T0 to T2 (G1 and G2 p < 0.01). In G2, 40.4% of individuals with osteopenia and osteoporosis presented inadequacy of 25(OH)D.

Conclusion

RYGB was found to worsen the inadequacy of micronutrients related to bone metabolism and was associated with secondary hyperparathyroidism and low BMD values, especially among the adolescents. The irreversible damaging effects of obesity on bone metabolism can occur in adolescence.

https://ift.tt/2Ubh07h

Loss of Control Eating and Binge Eating in the 7 Years Following Bariatric Surgery

Abstract

Background

Although bariatric surgery is an effective intervention for severe obesity, a subset of patients demonstrates suboptimal weight outcomes. Postoperative loss of control eating (LOCE) and binge eating may influence weight outcomes, though research has not examined differences by surgical procedure, or factors that predict postoperative LOCE. This study aimed to [1] characterize LOCE and binge eating disorder (BED) over a 7-year period following bariatric surgery; [2] examine concurrent, prospective, and cumulative relationships between LOCE and weight loss; [3] assess whether these associations are moderated by surgery type; and [4] evaluate predictors of LOCE.

Methods

Participants were 2156 patients who underwent laparoscopic adjustable gastric banding (LAGB) or Roux-n-Y gastric bypass (RYGB) in the multi-center Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study. Generalized linear mixed models examined relationships between LOCE and percent weight loss and predictors of LOCE.

Results

LOCE and BED initially declined then increased after surgery, with a notable number of de-novo cases (25.6% and 4.8%, respectively). LOCE was related to less concurrent but not prospective or cumulative percent weight loss. Self-monitoring of eating, higher daily eating frequency, older age, male gender, and higher self-esteem were associated with a lower likelihood of LOCE.

Conclusions

Results suggest that LOCE and binge eating are clinically relevant behaviors that may impede weight loss, and findings highlight the importance of ongoing assessment of maladaptive eating following surgery.

https://ift.tt/2BWAt4C

Excessive daytime sleepiness and its impact on quality of life in de novo Parkinson’s disease

Abstract

Excessive daytime sleepiness (EDS) is one of the most common sleep problems in patients with Parkinson's disease (PD); however, its clinical implications are not clear, especially in early stage, non-medicated PD patients. This study investigated EDS in Korean patients with de novo PD and its impact on quality of life. This cross-sectional study was carried out with 198 PD patients who underwent a structured clinical interview and examination based on common and conventional scales. Motor and nonmotor symptoms were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and Non-Motor Symptoms Scale (NMSS). EDS was evaluated with the Epworth Sleepiness Scale (ESS), the nocturnal disabilities and nighttime sleep problems were assessed with Parkinson's Disease Sleep Scale 2nd version, and quality of life was measured with the Parkinson's Disease Quality of Life 39 (PDQ-39). The relationships between ESS score and each scale were investigated. Among the patients studied, 42 patients had EDS defined as ESS > 10. Patients with EDS had a higher motor burden, greater nocturnal disabilities, more severe non-motor symptoms, and lower quality of life than did patients without EDS. Partial correlations revealed that ESS score was related to PDQ-39 summary index, irrespective of age, body mass index, or disease duration. These results show that EDS can have an immense negative impact on quality of life. The causes of EDS are multifactorial, which complicates its treatment. Further investigations are required to determine the safety and efficacy of potential EDS therapies and to develop novel EDS treatments in PD.

https://ift.tt/2GR8ZS6

EZH2 plays a crucial role in ischemia/reperfusion-induced acute kidney injury by regulating p38 signaling

Abstract

Objective and design

Renal ischemia–reperfusion (IR)-induced acute kidney injury (AKI) remains a major challenge in clinic. The histone methyltransferases enhancer of zest homolog-2 (EZH2) is associated with the development of renal injury. However, the molecular mechanism has not been fully elucidated.

Materials

AKI in C57BL/6 mice was generated by renal IR.

Treatments

The 3-deazaneplanocin A (DZNeP), a selective EZH2 inhibitor, or vehicle was administrated in mice after IR. HK-2 cells were exposed to hypoxia-reoxygenation (H/R) stress.

Methods

Apoptosis was detected by TUNEL assay or flow cytometry. EZH2, caspase-3, p38, F4/80⁺ macrophages, and CD3⁺ T cells were examined by immunohistochemistry or Western blot. Tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, IL-6, and IL-18 were measured using RT-PCR.

Results

Mice treated with DZNeP exhibited less severe renal dysfunction and tubular injury following IR. EZH2 inhibition decreased apoptotic cells while reducing activation of caspase-3 in kidneys under IR condition. Moreover, EZH2 inhibition impaired the recruitment of CD3⁺ T cells and F4/80⁺ cells in kidneys with IR. Administration of DZNeP suppressed the production of TNF-α, MCP-1, IL-6, and IL-18 in IR-treated kidneys. Of note, EZH2 inhibition reduced p38 phosphorylation in kidneys after IR. In H/R-treated HK-2 cells, DZNeP treatment or EZH2 knockdown reduced apoptosis. EZH2 inhibition inactivated p38 resulting in reduction of active caspase-3 and proinflammatory molecules. By contrast, EZH2 overexpression induced p38 phosphorylation, caspase-3 activation, and production of proinflammatory molecules, which was reversed by SB203580.

Conclusions

EZH2 plays a crucial role in IR-induced AKI via modulation of p38 signaling. Targeting EZH2/p38 signaling pathway may offer novel strategies to protect kidneys from acute kidney injury induced by ischemia–reperfusion.

https://ift.tt/2Xtcovl

Charge transference and conformational stress influence on the electronic properties of zigzag carbon nanowires

Abstract

The structural and electronic properties of nanostructures resulting from the insertion of a linear carbon chain (LCC) into a semiconducting zigzag single-walled carbon nanotubes (SWCNTs) were studied using density functional theory. Although all isolated constituents exhibited a semiconductor behavior, semiconductor transitions to metallic character were found in the combined system. The competitive effects on the band gap due to the conformational stress and charge transfer were analyzed, both resulting in an overall metallic character. The electronic character in nanowires with (7,0) nanotube is affected by structural strain and charge transfer with a slightly higher influence of the charge transferred. Nanowires with (8,0) nanotube and bigger are mainly affected by strain, and their electronic states distribution retains the energy gap associated with isolated semiconducting nanotube with only a few empty states slightly above the Fermi level due to the charge transfer to LCC. A metallic behavior was found for all nanowires. However, a metallization dependence with nanotube diameters was found. LCC shows a metallic contribution in all cases. This study suggests that strain could produce nanostructures with a global metallic behavior which is provided by a metallic LCC plus a semiconducting nanotube for sizes as small as 6.5 Å. Zigzag nanowires smaller than this last value produce strained LCC accompanied by a transition from semiconductor to metal on both subsystems.

https://ift.tt/2NzFDIe

The association between obstructive sleep apnea syndrome and metabolic syndrome: a confirmatory factor analysis

Abstract

Background

Growing evidence suggests an independent relationship between obstructive sleep apnea syndrome (OSAS) and metabolic syndrome (MS). Patients with OSAS always show clustering of metabolic components. However, the understanding of interplay between OSAS and metabolic components is still lacking.

Methods

Participants were consecutively enrolled from our sleep center during the period 2009–2013. Anthropometric variables, metabolic indicators, and sleep parameters were collected from all participants. The factor structure for MS in OSAS and non-OSAS was examined by confirmatory factor analysis.

Results

The OSAS and non-OSAS demonstrated clustering of metabolic components. MS in patients with OSAS was strongly associated with insulin resistance (standardized factor loading = 0.93, p < 0.001), obesity (loading = 0.92, p < 0.001), and the lipid profile (loading = 0.72, p < 0.001). Furthermore, insulin resistance was correlated with obesity and lipid profile (r = 0.86, p < 0.001; r = 0.68, p < 0.001, respectively). Obesity and lipid profile were also highly correlated in OSAS (r = 0.66, p < 0.001). In non-OSAS, MS was strongly associated with insulin resistance, obesity, and lipid profile (loading = 0.95, p < 0.001; loading = 0.74, p < 0.001; loading = 0.68, p < 0.001, respectively). Insulin resistance was most strongly associated with fasting insulin (loading = 0.65, p < 0.001). Lipid profile was most strongly associated with TG (loading = 0.88, p < 0.001). Obesity was most strongly associated with BMI (loading = 0.80, p < 0.001).

Conclusions

OSAS is more prone to show clustering of metabolic components compared with non-OSAS. In particular, insulin resistance, obesity, and the lipid profile were independently and strongly correlated with MS in OSAS.

https://ift.tt/2tIDPDW

Population pharmacokinetic analysis of AR-67, a lactone stable camptothecin analogue, in cancer patients with solid tumors

Summary

Background AR-67 is a novel camptothecin analogue at early stages of drug development. The phase 1 clinical trial in cancer patients with solid tumors was completed and a population pharmacokinetic model (POP PK) was developed to facilitate further development of this investigational agent. Methods Pharmacokinetic data collected in the phase 1 clinical trial were utilized for the development of a population POP PK by implementing the non-linear mixed effects approach. Patient characteristics at study entry were evaluated as covariates in the model. Subjects (N = 26) were treated at nine dosage levels (1.2–12.4 mg/m²/day) on a daily × 5 schedule. Hematological toxicity data were modeled against exposure metrics. Results A two-compartment POP PK model best described the disposition of AR-67 by fitting a total of 328 PK observations from 25 subjects. Following covariate model selection, age remained as a significant covariate on central volume. The final model provided a good fit for the concentration versus time data and PK parameters were estimated with good precision. Clearance, inter-compartmental clearance, central volume and peripheral volume were estimated to be 32.2 L/h, 28.6 L/h, 6.83 L and 25.0 L, respectively. Finally, exposure-pharmacodynamic analysis using E_max models showed that plasma drug concentration versus time profiles are better predictors of AR-67-related hematologic toxicity were better predictors of leukopenia and thrombocytopenia, as compared to total dose. Conclusions A POP PK model was developed to characterize AR-67 pharmacokinetics and identified age as a significant covariate. Exposure PK metrics C_max and AUC were shown to predict hematological toxicity. Further efforts to identify clinically relevant determinants of AR-67 disposition and effects in a larger patient population are warranted.

https://ift.tt/2NxfsC8

Correction to: Genetic Evidence of Middle East Respiratory Syndrome Coronavirus (MERS-Cov) and Widespread Seroprevalence among Camels in Kenya

The acknowledgement section in the original article was published incorrectly.

https://ift.tt/2T5amTz

Mesenchymal stem cell transplantation in polytrauma: Evaluation of bone and liver healing response in an experimental rat model

Abstract

Purpose

Trauma is the most common cause of death of young people in the world. As known, mesenchymal stem cells (MSCs) accelerate tissue regeneration mechanisms. In our study, we aimed to investigate the effects of MSCs transplantation on the healing of liver and bone tissue by considering trauma secondary inflammatory responses.

Methods

56 adult Wistar-albino rats were divided into two groups: the polytrauma (liver and bone) (n = 28), and the liver trauma group (n = 28). At 36 h and 5th day after surgery, both rats with polytrauma and with isolated liver injury received either intravenous (IV) or intraperitoneal (IP) injections of MSCs (one million cells per kg body weight). Untreated groups received IV and IP saline injections. At day 21 after surgery, liver, tibia and fibula of the subjects were excised and evaluated for histopathologic and histomorphometric examination. Additionally, whole blood count (white blood cells, hemoglobin and platelets), C-reactive protein (CRP), glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, blood gas, and trauma markers interleukin-1B (IL-1B), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) levels were investigated.

Results

In general, MSC transplantations were well tolerated by the subjects. It was found that ALT, CRP, albumin were significantly lower in rats which received MSCs (p < 0.001). Inflammation of the liver and bone tissue in the MSC-injected rats were significantly lower than that of the untreated groups.

Conclusions

Herewith we have shown that MSC infusion in posttraumatic rats leads to less aggressive and more effective consequences on liver and bone tissue healing. Human MSC treatment for trauma is still in early stages of development; thus standard protocols, and patient inclusion criteria should be established beforehand clinical trials.

https://ift.tt/2Ej6G6t

Total knee arthroplasty for distal femoral fractures in osteoporotic bone: a systematic literature review

Abstract

Purpose

Distal femoral fractures in the elderly are associated with high morbidity and mortality and their incidence is increasing with an ageing population. Management of these fractures has evolved over recent decades and there is now an accepted recognition of the important role that acute arthroplasty may have in treatment of these fractures. Our purpose was to systematically review the evidence available in the literature for arthroplasty as a treatment option for distal femoral fractures.

Methods

This systematic review was conducted in accordance with the PRISMA reporting guidelines. We searched CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded (until October 2018) for studies and case series. Furthermore, clinical trial registries were searched for ongoing studies. We included all studies or case series that described total knee arthroplasty for distal femoral fractures irrespective of language, publication status, sample size, or follow-up period due to limited studies available in the literature. Exclusion criteria included single patient case reports, isolated tibia fractures, and periprosthetic fractures. Two authors independently identified trials for inclusion and independently extracted the data. Outcome measures included mortality, peri-operative complications (excluding mortality), anaesthetic time, blood loss, time to mobilisation, length of hospital stay, functional scores, radiological loosening, and revision rate.

Results

Fourteen papers were included for subsequent quantitative and qualitative synthesis incorporating a total of 181 patients. The highest level of evidence identified was a single cohort study (level III), the remaining 13 papers consisted of multi- or single-centre case series (level IV). The mean mortality rate was 3.34% (range 0–10) at 30 days and 18.4% (range 0–42) at 1 year. The mean revision rate was 3.43% (range 0–25) at 1 year. The mean time to mobilisation was 3.90 days (range 2.5–6) with a mean time to discharge from the acute ward being 16.6 days (range 8–33).

Conclusions

Although there is limited evidence in the literature available, our review suggests that there is a role for acute knee arthroplasty in distal femoral fractures. This mode of treatment has satisfactory mortality and revision rates, and may result in faster time to mobilisation and discharge. There is a need for a higher level of evidence to delineate this issue further.

https://ift.tt/2T2bUOl

Factors predicting adverse outcome in complete intra-articular distal radius fractures

Abstract

Purpose

To determine risk factors associated with adverse functional and radiological outcome in complete intra-articular distal radius fractures (AO 23 C2–3) with a minimum follow-up of 1 year.

Methods

Retrospective case series of 87 consecutive patients with a complete intra-articular distal radius fracture (AO/OTA 23 C2–3) and a minimum follow-up of 1 year between 2012 and 2016. Risk factors for adverse clinical [using the Patient-Rated Wrist Evaluation (PRWE) score] and radiological outcome (positive ulnar variance 1 year postoperative) were analysed in a linear regression model.

Results

PRWE scored a median of 4.5 points (range 0–72.5) after a median follow-up of 31 months (range 12–70 months). A concomitant polytrauma was associated with a worse PRWE (β = 23.34, p < 0.01) and was also significantly associated with the use of a temporary external fixator (χ² = 11.93; p < 0.01) and high-energy trauma (χ² = 19.39; p < 0.01). Radiological outcome measures 1 year postoperative did not correlate with clinical outcome measures.

Conclusion

This cohort of complete intra-articular distal radius fractures (AO/OTA 23 C2–3) shows a good clinical outcome at medium-term follow-up independent of the radiological outcome. A concomitant polytrauma was associated with worse functional outcome and a higher complication rate. This is most likely due to the associated injury severity. These factors help the treating physician in decision-making and informing patients when treating displaced intra-articular radius fractures.

https://ift.tt/2EdwiBC

Anti-CGRP in cluster headache therapy

Abstract

Cluster headache is a primary headache characterized by recurring excruciating pain and autonomic signs, leading to significant suffering and derangement of patients' life. Efficacious new preventive treatments are needed. The pathophysiology of cluster headache comprises mechanisms both in the peripheral and central nervous system, involving the trigeminovascular system, the trigemino-parasympathetic reflex, and central modulating systems. Calcitonin gene–related peptide (CGRP) has an active role throughout these systems. It is increased during spontaneous and provoked attacks, and itself can induce attacks. Recently, drugs against this neuropeptide have been developed for the treatment of different headache disorders. In particular, monoclonal antibodies vs CGRP as galcanezumab and fremanezumab have been tested in cluster headache, with promising results for the episodic form. Considering the relevance of central mechanisms in CH, drugs interfering with the CGRP pathway in the central nervous system can enlarge the therapeutic armamentarium against this highly disabling condition.

https://ift.tt/2StbaMV

AGEs induce epithelial to mesenchymal transformation of human peritoneal mesothelial cells via upregulation of STAT3

Abstract

Epithelial-mesenchymal transition (EMT) in peritoneum was induced during peritoneal dialysis (PD), which finally caused progressive fibrosis. However, the underlying mechanisms were not well elucidated. We established advanced glycation end-products (AGEs)-induced EMT model using primary human peritoneal mesothelial cells (HPMCs). The working concentration and time of AGEs were optimized. Then the expression and activation signal transducer and activator of transcription 3 (STAT3), a key factor of EMT in cancer, were detected. The regulation of STAT3 by miRNA was also explored. 50 μg/ml AGEs treatment for 24 h can successfully induce EMT in HPMCs. AGEs treatment upregulated and activated STAT3. miRNA-454, potentially targeting STAT3, was down-regulated in AGEs-treated HPMCs. Overexpression of miRNA-454 prevented AGEs- induced EMT in HPMCs. AGEs induce epithelial to mesenchymal transformation of Human peritoneal mesothelial cells via upregulation of STAT3.

https://ift.tt/2NwQgvC

Body Contouring Following Massive Weight Loss: the Evolving Role of Plastic Surgeons and Risk Stratification Tools

https://ift.tt/2GPkcCA

Effects of Preventive Treadmill Exercise on the Recovery of Metabolic and Mitochondrial Factors in the 6-Hydroxydopamine Rat Model of Parkinson’s Disease

Abstract

Metabolic and mitochondrial dysfunction has been implicated in Parkinson's disease, while exercise can induce essential pathways of mitochondrial biogenesis. Here, we tested whether long-term preventive treadmill training (16 weeks, 21 m/min, and 0° inclinations for 50 min/d, 5 d/week) effects the mitochondrial and neurodegeneration markers, in the striatum of rats in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Following 16 weeks of exercise or no exercise period (n = 16 rats per group), the animals were divided into four experimental groups (n = 8 per group): (1) no exercise and saline (SED), (2) exercise and saline (EX), (3) no exercise and 6-OHDA (SED + 6-OHDA), and (4) exercise and 6-OHDA (EX + 6-OHDA). For the model, 8 μg of 6-OHDA (2 μg/μL prepared in a solution of 0.2% ascorbic acid and 0.9% saline) was injected into the right medial forebrain bundle. Exposure to 6-OHDA resulted in a significant reduction (P < 0.05) of mitochondrial factors AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma coactivator-1 alpha, and tyrosine hydroxylase, and increased expression of silent information regulator T1, mitochondrial transcription factor A, and p53 in the SED + 6-OHDA group relative to SED group. By contrast, gene and protein expressions upon exercise were higher and p53 protein level was lower in the EX + 6-OHDA group compared with SED + 6-OHDA. Further, exercise reduced the extent of weight loss associated with the 6-OHDA injection. In conclusion, exercise might be used to reduce mitochondrial disorders in Parkinson's disease.

https://ift.tt/2tGyCMP

Salicylate-Induced Ototoxicity of Spiral Ganglion Neurons: Ca 2+ /CaMKII-Mediated Interaction Between NMDA Receptor and GABA A Receptor

Abstract

Sodium salicylate (SS) is one of the nonsteroidal anti-inflammatory drugs and widely used in clinical practice. Therefore, we aimed to investigate the potential ototoxicity mechanism of sodium salicylate: the influence of Ca²⁺/calmodulin-dependent protein kinase II (Ca²⁺/CaMKII) in interaction between NMDA receptors (NMDAR) and GABA_A receptors (GABA_AR) in rat cochlear spiral ganglion neurons (SGNs). After treatment with SS, NMDA, and an NMDAR inhibitor (APV), the changes of GABA_AR β3 (GABR β3) mRNA, surface and total protein, and GABA_AR currents in SGNs were assessed by quantitative PCR, Western blot, and whole-cell patch clamp. Mechanistically, SS and/or NMDA increased the GABR β3 mRNA expression, while decreased GABR β3 surface protein levels and GABA_AR-mediated currents. Moreover, application of SS and/or NMDA showed promotion in phosphorylation levels at S383 of GABR β3. Collectively, Ca²⁺ chelator (BAPTA) or Ca²⁺/CaMKII inhibitor (KN-93) reversed the effects of SS and/or NMDA on GABA_AR. Therefore, we hypothesize that the interaction between NMDAR and GABA_AR is involved in the SGNs damage induced by SS. In addition, the underlying molecular mechanism is related to Ca²⁺/CaMKII-mediated signaling pathway, which suggests that the interaction between calcium signal-regulated receptors mediates SS ototoxicity.

https://ift.tt/2H8Jg6L

Chylous fistula: management of a rare complication following right anterior cervical spine approach

Abstract

Purpose

Chylorrhea resulting from injury of the lymphatic system during neck dissection is a well-known complication. It is an uncommon occurrence in spinal surgery, and only one case after right anterior cervical spine surgery has been described so far. Despite its rarity, chylous leakage deserves a particular attention since it may become a serious and occasionally fatal complication if not detected early and managed appropriately.

Methods

We report the case of a 42-year-old man who underwent a standard anterior cervical discectomy and fusion according to Cloward approach for a C6–C7 disk herniation. The patient developed a delayed prevertebral chyle collection on postoperative day 5, presenting with mild breathing and swallowing difficulties.

Results

He was managed with conservative care, including bed rest, low-fat diet and drainage pouch positioning, which led to the complete resolution of the fluid collection.

Conclusions

Knowledge of the normal anatomy of the lymphatic system and of its variations is essential when planning an anterior spinal procedure, and represents the first measure to be adopted in order to avoid such complication. The prompt identification of a postoperative chylous fistula and the applicability of an individually based management's protocol may help in the majority of the cases to reduce the potential morbidity, without significant long-term effects.

https://ift.tt/2ElKdWi

Thermally stable and dielectric nanocomposite based on poly(arylene ether nitrile) and BaTiO 3 functionalized by modified mussel-inspired route

Abstract

Easy and efficient surface functionalization is critical for obtaining high-performance barium titanate (BaTiO₃) based dielectric polymer composites. We here demonstrated the easy surface functionalization of barium titanate via modified mussel-inspired method, using dopamine and silane coupling agent KH550 as reactive precursors. As-modified BaTiO₃ hybrid presented core-shell structure, which was further compounded with thermally stable poly(arylene ether nitrile)(PEN) via simple solution casting method, thus obtaining dielectric nanocomposite films. As a result, the dielectric constant of PEN was enhanced from 3.5 to 10.7 at 1 KHz by addition of 40 wt% BaTiO₃ hybrid, due to good dispersion of BaTiO₃ nanoparticles and its interfacial interaction with PEN matrix. Furthermore, as-prepared PEN composites exhibited low dielectric loss, which fluctuated in the range of 0.03 to 0.11 at 1 KHz. Besides, the thermal stability of PEN was significantly improved, and the tensile strength was well maintained even the weight ratio of BaTiO₃ hybrid reached 40 wt%. Therefore, thermally stable and dielectric PEN composite films show promising application in special area where high thermal stability, high strength, and high dielectric constant are needed.

https://ift.tt/2EhajKd

Population pharmacokinetic analysis of AR-67, a lactone stable camptothecin analogue, in cancer patients with solid tumors

Summary

Background AR-67 is a novel camptothecin analogue at early stages of drug development. The phase 1 clinical trial in cancer patients with solid tumors was completed and a population pharmacokinetic model (POP PK) was developed to facilitate further development of this investigational agent. Methods Pharmacokinetic data collected in the phase 1 clinical trial were utilized for the development of a population POP PK by implementing the non-linear mixed effects approach. Patient characteristics at study entry were evaluated as covariates in the model. Subjects (N = 26) were treated at nine dosage levels (1.2–12.4 mg/m²/day) on a daily × 5 schedule. Hematological toxicity data were modeled against exposure metrics. Results A two-compartment POP PK model best described the disposition of AR-67 by fitting a total of 328 PK observations from 25 subjects. Following covariate model selection, age remained as a significant covariate on central volume. The final model provided a good fit for the concentration versus time data and PK parameters were estimated with good precision. Clearance, inter-compartmental clearance, central volume and peripheral volume were estimated to be 32.2 L/h, 28.6 L/h, 6.83 L and 25.0 L, respectively. Finally, exposure-pharmacodynamic analysis using E_max models showed that plasma drug concentration versus time profiles are better predictors of AR-67-related hematologic toxicity were better predictors of leukopenia and thrombocytopenia, as compared to total dose. Conclusions A POP PK model was developed to characterize AR-67 pharmacokinetics and identified age as a significant covariate. Exposure PK metrics C_max and AUC were shown to predict hematological toxicity. Further efforts to identify clinically relevant determinants of AR-67 disposition and effects in a larger patient population are warranted.

https://ift.tt/2NxfsC8

Prevalence and Factors Associated with Visiting the Dentist Only for Emergency Care Among Indigenous People in Ontario

Abstract

Ontario has the largest Indigenous population in Canada. This study aims to examine the prevalence and factors associated with poor dental care use amongst the Indigenous in Ontario. Data from the 2014 cycle of the Canadian Community Health Survey was used. The main outcome was defined as visiting the dentist only for emergency care. Stepwise multivariable logistic regression was performed to assess the association between socio-demographic, socio-economic, and the health related factors and emergency dental care use. 28% of the participants reported visiting the dentist only for emergencies. First Nations people were at increased odds of having poor dental care (OR 2.01, CI 1.12–3.95). Additionally, being male, a smoker, having fair/poor health and lacking dental insurance puts the Indigenous Ontarians at increased odds of having the outcome. Improvements to the current social benefit programs could help better cater to the needs of this population.

https://ift.tt/2TgpJbe

Short- and long-term continuous positive airway pressure usage in the post-stroke population with obstructive sleep apnea

Abstract

Purpose

Obstructive sleep apnea (OSA) is highly prevalent in post-stroke patients and observational evidence suggests that untreated it is a harbinger of poorer outcomes in this population. Clinical trials on the impact of treatment of OSA with continuous positive airway pressure (CPAP) have countered difficulties with patient engagement and adherence to CPAP therapy. Real-world data on continuous positive airway pressure initiation and usage in the post-stroke population with obstructive sleep apnea is limited.

Methods

We performed a clinical retrospective study between January 2006 and June 2015 to describe the short- and long-term CPAP usage in the post-stroke population with OSA, and to assess which patient, disease, and treatment-related factors were associated with CPAP purchase, initiation, and usage in this population.

Results

Of 191 post-stroke patients' recommended CPAP therapy, post-prescription usage at 3, 6, 12, 24, and 60 months was 58%, 53%, 48%, 45%, and 39% respectively. OSA severity-related factors, such as AHI or degree of nocturnal hypoxemia, were not significantly associated with CPAP usage. Predictors of CPAP usage at all time points were younger age, male sex, never smokers, and no history of hypertension. There were some differences in predictors of CPAP usage between early and later time periods.

Conclusions

We demonstrated that the long-term usage of CPAP therapy is possible with most of the attrition occurring in the first 3 months. Upfront healthcare resource allocation to CPAP initiation and usage in this population may improve longer-term usage.

https://ift.tt/2ECevpn

Transition of inner cell mass to embryonic stem cells: mechanisms, facts, and hypotheses

Abstract

Embryonic stem cells (ESCs) are immortal stem cells that own multi-lineage differentiation potential. ESCs are commonly derived from the inner cell mass (ICM) of pre-implantation embryos. Due to their tremendous developmental capacity and unlimited self-renewal, ESCs have diverse biomedical applications. Different culture media have been developed to procure and maintain ESCs in a state of naïve pluripotency, and to preserve a stable genome and epigenome during serial passaging. Chromatin modifications such as DNA methylation and histone modifications along with microRNA activity and different signaling pathways dynamically contribute to the regulation of the ESC gene regulatory network (GRN). Such modifications undergo remarkable changes in different ESC media and determine the quality and developmental potential of ESCs. In this review, we discuss the current approaches for derivation and maintenance of ESCs, and examine how differences in culture media impact on the characteristics of pluripotency via modulation of GRN during the course of ICM outgrowth into ESCs. We also summarize the current hypotheses concerning the origin of ESCs and provide a perspective about the relationship of these cells to their in vivo counterparts (early embryonic cells around the time of implantation). Finally, we discuss generation of ESCs from human embryos and domesticated animals, and offer suggestions to further advance this fascinating field.

https://ift.tt/2Ud2NH1

Heparan sulfate proteoglycan (HSPG) can take part in cell division: inside and outside

Abstract

Prior to the cytokinesis, the cell–matrix interactions should be disrupted, and the mitotic cells round up. Prerequisite of mitosis, the centrosomes duplicate, spindle fibers are generated and move away from each other to opposite sides of the cells marking the cell poles. Later, an invagination in the plasma membrane is formed a few minutes after anaphase. This furrow ingression is driven by a contractile actomyosin ring, whose assembly is regulated by RhoA GTPase. At the completion of cytokinesis, the two daughter cells are still connected by a thin intercellular bridge, which is subjected to abscission, as the terminal step of cytokinesis. Here, it is overviewed, how syndecan-4, a transmembrane, heparan sulfate proteoglycan, can contribute to these processes in a phosphorylation-dependent manner.

https://ift.tt/2BWp193

Transcription factor Ptf1a in development, diseases and reprogramming

Abstract

The transcription factor Ptf1a is a crucial helix–loop–helix (bHLH) protein selectively expressed in the pancreas, retina, spinal cord, brain, and enteric nervous system. Ptf1a is preferably assembled into a transcription trimeric complex PTF1 with an E protein and Rbpj (or Rbpjl). In pancreatic development, Ptf1a is indispensable in controlling the expansion of multipotent progenitor cells as well as the specification and maintenance of the acinar cells. In neural tissues, Ptf1a is transiently expressed in the post-mitotic cells and specifies the inhibitory neuronal cell fates, mostly mediated by downstream genes such as Tfap2a/b and Prdm13. Mutations in the coding and non-coding regulatory sequences resulting in Ptf1a gain- or loss-of-function are associated with genetic diseases such as pancreatic and cerebellar agenesis in the rodent and human. Surprisingly, Ptf1a alone is sufficient to reprogram mouse or human fibroblasts into tripotential neural stem cells. Its pleiotropic functions in many biological processes remain to be deciphered in the future.

https://ift.tt/2UayuRm

Mitochondrial functions and melatonin: a tour of the reproductive cancers

Abstract

Cancers of the reproductive organs have a strong association with mitochondrial defects, and a deeper understanding of the role of this organelle in preneoplastic–neoplastic changes is important to determine the appropriate therapeutic intervention. Mitochondria are involved in events during cancer development, including metabolic and oxidative status, acquisition of metastatic potential, resistance to chemotherapy, apoptosis, and others. Because of their origin from melatonin-producing bacteria, mitochondria are speculated to produce melatonin and its derivatives at high levels; in addition, exogenously administered melatonin accumulates in the mitochondria against a concentration gradient. Melatonin is transported into tumor cell by GLUT/SLC2A and/or by the PEPT1/2 transporters, and plays beneficial roles in mitochondrial homeostasis, such as influencing oxidative phosphorylation and electron flux, ATP synthesis, bioenergetics, calcium influx, and mitochondrial permeability transition pore. Moreover, melatonin promotes mitochondrial homeostasis by regulating nuclear DNA and mtDNA transcriptional activities. This review focuses on the main functions of melatonin on mitochondrial processes, and reviews from a mechanistic standpoint, how mitochondrial crosstalk evolved in ovarian, endometrial, cervical, breast, and prostate cancers relative to melatonin's known actions. We put emphasis on signaling pathways whereby melatonin interferes within cancer-cell mitochondria after its administration. Depending on subtype and intratumor metabolic heterogeneity, melatonin seems to be helpful in promoting apoptosis, anti-proliferation, pro-oxidation, metabolic shifting, inhibiting neovasculogenesis and controlling inflammation, and restoration of chemosensitivity. This results in attenuation of development, progression, and metastatic potential of reproductive cancers, in addition to lowering the risk of recurrence and improving the life quality of patients.

https://ift.tt/2BWp0C1

Modeling elastin-associated vasculopathy with patient induced pluripotent stem cells and tissue engineering

Abstract

Elastin-associated vasculopathies are life-threatening conditions of blood vessel dysfunction. The extracellular matrix protein elastin endows the recoil and compliance required for physiologic arterial function, while disruption of function can lead to aberrant vascular smooth muscle cell proliferation manifesting through stenosis, aneurysm, or vessel dissection. Although research efforts have been informative, they remain incomplete as no viable therapies exist outside of a heart transplant. Induced pluripotent stem cell technology may be uniquely suited to address current obstacles as these present a replenishable supply of patient-specific material with which to study disease. The following review will cover the cutting edge in vascular smooth muscle cell modeling of elastin-associated vasculopathy, and aid in the development of human disease modeling and drug screening approaches to identify potential treatments. Vascular proliferative disease can affect up to 50% of the population throughout the world, making this a relevant and critical area of research for therapeutic development.

https://ift.tt/2U7n0xX